Prophylaxis of Venous Thromboembolism Clinical Trial
Official title:
Pharmacokinetics and Pharmacodynamics of Single Doses of Rivaroxaban in Obesity Patients Before and After Bariatric Surgery
Until now there ist no systematic investigation of the pharmacokinetic parameters of
Rivaroxaban in obese patient undergoing bariatric surgery. The aim of this study is to
investigate the pharmacokinetic and pharmacodynamic parameters of rivaroxaban in obese
patients before and after bariatric surgery.
Patients receive the day before the surgical intervention the first dose of Rivaroxaban
(10mg). During the following 24 hours, 9 blood samples are taken.
The second tablet Rivaroxaban is administered on the third postoperative day, followed again
by 9 blood samples during the next 24 hours.
All other blood samples are taken independent from this clinical trial as part of the
standard medical treatment during the hospitalization. The hospital stay will not be
extended by the study. The outpatient regular follow-up takes place one month after surgery
and is combined with the last study visit.
Background
The prevalence of obesity and morbid obesity is increasing worldwide and is becoming an
increasing medical and socioeconomic burden. Bariatric surgery leads to the most sustained
reduction of weight and associated co-morbidities. Obesity is a risk factor for the
development of venous thromboembolism and the association between obesity and postoperative
VTE is well established. The incidence of symptomatic DVT and PE ranges from 0%-5.4%,
respectively 0%-6.4% and remains uncertain. Although the overall incidence seems to be low,
VTE represents a significant cause of morbidity and mortality after surgery. Most
postdischarge VTE events occur within the first 30 days after surgery and therefore extended
chemoprophylaxis after hospital discharge is the standard of care and should be considered
especially for patients classified to be at high risk for VTE.
Anticoagulants are recommended for the prevention of VTE, but there is no consensus
regarding optimal method of prophylaxis. Routine perioperative use of drugs such as
low-molecular weight heparins (LMWHs), intermittent pneumatic compression and early
mobilization are currently the major accepted forms. However, there is currently no class I
evidence to provide guidance regarding the type or dose of antithrombotic prophylaxis after
bariatric surgery. For parenteral application there is for example limited evidence to guide
dosing of thromboprophylaxis in morbid obesity and higher dosages are necessary, because
impaired absorption after subcutaneous application.
The knowledge of the effect of extremely high body weight on pharmacokinetic and
pharmacodynamics parameters after bariatric surgery especially for novel orally administered
anticoagulants that target specific factors in the coagulation cascade is scarce. One
promising therapeutic option is rivaroxaban (BAY 59-7939, Rivaroxaban), an orally
administered direct factor Xa inhibitor that is approved for several indications in the
field of prevention and treatment of thromboembolic disorders.
In several types of bariatric surgery procedures, such as sleeve gastrectomy, Roux-en-Y
gastric bypass and biliopancreatic diversion different parts of gastrointestinal tract are
bypassed or removed. This could affect the absorption of medications. Absorption of
rivaroxaban is dependent on the site of drug release in the GI tract. In a study looking at
administration of the crushed tablet via a tube, a 29% and 56% decrease in AUC and Cmax
compared to an oral tablet was reported when rivaroxaban granulate is released in the
proximal small intestine. The effect of altered anatomy due to RYGB on oral drug absorption
and bioavailability is currently unknown. Previous studies focused on drugs like metformin,
sertraline or tacrolimus, but they yielded conflicting results. In a case report by Mahlmann
et al. the absorption of rivaroxaban was immediate and not significantly impaired by
bariatric surgery of the upper GI tract. However, data from larger patient collectives are
not available.
Rivaroxaban is already approved for VTE prophylaxis in orthopaedic patients. Up to now,
there is no clinical data available regarding obese patients after bariatric surgery. To
fill this gap, this phase 1 clinical trial was designed with a study design that allows for
intra-patient comparison of the effect of the bariatric surgery regarding pharmacokinetic
and pharmacodynamics analysis.
Rivaroxaban as an oral anticoagulant could be an attractive option for VTE prophylaxis
compared to subcutaneous (LMWH) standard treatment after bariatric surgery. Especially
high-risk patients (high BMI, a history of DVT, obesity hypoventilation syndrome, pulmonary
hypertension, hormonal therapy, venous stasis disease, male gender, expected long operative
time or open approach, where an extended duration of thromboprophylaxis after hospital
discharge is recommended, an oral therapy would be attractive.
Until now there is no systematic investigation of pharmacokinetic parameters of rivaroxaban
in obese patient undergoing bariatric surgery. This phase I clinical trial offers the unique
opportunity to investigate PK/PD in morbidly obese patients pre and post bariatric surgery.
The results of this trial will help to design larger trials in this particular patient
population with the final goal of safe and efficient use of rivaroxaban in morbidly
patients.
Objective
The aim of this study is to investigate the pharmacokinetic and pharmacodynamic parameters
of rivaroxaban in obese patients before and after bariatric surgery.
Methods
Investigation of rivaroxaban AUC in bariatric.
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Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02832947 -
PK of Rivaroxaban in Bariatric Patients - Extension
|
Phase 1 |